Evidence map›Paper›PMID 27110488›Full record

ArticleMolecular metabolism2016

Inter-domain tagging implicates caveolin-1 in insulin receptor trafficking and Erk signaling bias in pancreatic beta-cells.

Tobias Boothe, Gareth E Lim, Haoning Cen, Søs Skovsø, Micah Piske, Shu Nan Li, Ivan R Nabi, Patrick Gilon, James D Johnson

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Molecular metabolism, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.

0numbers the graph read from it
0cells of the map it votes in
31citing papers in PubMed
3.2field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

31 citing papers in PubMed, 49 citations in OpenAlex.

  1. Article
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  6. Article
  7. Serotonin Influences Insulin Secretion in Rat Insulinoma INS-1E Cells.International journal of molecular sciences · 2024
    Article
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  12. Article
  13. Poly(ADP-ribose) Polymerase 1 Mediates Rab5 Inactivation after DNA Damage.International journal of molecular sciences · 2022
    Article
  14. Article
  15. Article
  16. Revising Endosomal Trafficking under Insulin Receptor Activation.International journal of molecular sciences · 2021
    Review
  17. Article
  18. Article
  19. Sustained Stimulation of βDiabetes, metabolic syndrome and obesity : targets and therapy · 2020
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 2 countries.

Tobias BootheDepartment of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
Gareth E LimDepartment of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
Haoning CenDepartment of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
Søs SkovsøDepartment of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
Micah PiskeDepartment of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
Shu Nan LiDepartment of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
Ivan R NabiDepartment of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada.
Patrick GilonPôle d'endocrinologie, diabète et nutrition, Institut de recherche expérimentale et clinique, Université catholique de Louvain, Brussels, Belgium.
James D JohnsonDepartment of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada. Electronic address: James.D.Johnson@ubc.ca.
University of British Columbia · CAUCLouvain · BE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveThe role and mechanisms of insulin receptor internalization remain incompletely understood. Previous trafficking studies of insulin receptors involved fluorescent protein tagging at their termini, manipulations that may be expected to result in dysfunctional receptors. Our objective was to determine the trafficking route and molecular mechanisms of functional tagged insulin receptors and endogenous insulin receptors in pancreatic beta-cells.

methodsWe generated functional insulin receptors tagged with pH-resistant fluorescent proteins between domains. Confocal, TIRF and STED imaging revealed a trafficking pattern of inter-domain tagged insulin receptors and endogenous insulin receptors detected with antibodies.

resultsSurprisingly, interdomain-tagged and endogenous insulin receptors in beta-cells bypassed classical Rab5a- or Rab7-mediated endocytic routes. Instead, we found that removal of insulin receptors from the plasma membrane involved tyrosine-phosphorylated caveolin-1, prior to trafficking within flotillin-1-positive structures to lysosomes. Multiple methods of inhibiting caveolin-1 significantly reduced Erk activation in vitro or in vivo, while leaving Akt signaling mostly intact.

conclusionsWe conclude that phosphorylated caveolin-1 plays a role in insulin receptor internalization towards lysosomes through flotillin-1-positive structures and that caveolin-1 helps bias physiological beta-cell insulin signaling towards Erk activation.

Indexed as

Autocrine insulin signalingInsulin receptor internalizationInsulin resistancePancreatic islet beta-cells

Identifiers

PMID27110488
PMCPMC4837300
OpenAlexW2270265950

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.